Streptococcus pneumoniae is an important human pathogen and a major cause of morbidity and mortality in humans. Available pneumococcal vaccines consist of the purified PPS of the most common serotypes of S. pneumoniae that cause disease in adults and children. The rationale underlying pneumococcal vaccination is that type-specific antibodies to pneumococcal capsular polysaccharide (PPS) are required for protection.
However, PPS is poorly immunogenic in many individuals who are at the highest risk for the development of invasive pneumococcal disease, such as young children and immunocompromised individuals. The poor immunogenicity of PPS in infants and young children has been partly overcome by PPS-protein conjugate vaccines, but both conjugated and unconjugated pneumococcal vaccines are poorly immunogenic in many adults. Poor pneumococcal vaccine responses are most common in individuals with antibody defects or deficiency, but the mechanism responsible for this phenomenon is unknown. Accordingly, there is an urgent need for human antibodies for passive immunization of such individuals.
Currently, a limited number of human monoclonal antibodies to a limited number of PPS serotypes have been generated by Epstein-Barr virus transformation of lymphocytes from vaccinated recipients. Epstein-Barr virus transformation is difficult and unpredictable.
We provide human antibodies specific for S. pneumoniae PPS-3. Specifically, we provide monoclonal antibodies 1F10/7C5, 3H1, 1A2 and A7 which recognize S. pneumoniae PPS-3. Monoclonal antibodies 1F10/7C5, 1A2 and A7 effectively protect against S. pneumoniae challenge in passive immunizations.